The formation of physically uniform and chemically homogeneous spherical frozen particles from aqueous biological solutions and suspensions is essential to the manufacture of unit dose tablets for the pharmaceutical and diagnostic industries. Physically uniform particles minimize variability in bulk density and provide for tablet manufacturing processes that can produce tablets which vary in weight by no more than about one-half percent. Homogeneous chemical composition of the particles is needed to insure an accurate unit dose. From a manufacturing perspective it is desirable for frozen particles which are processed in various types of manufacturing tablet making equipment to exhibit the free flow properties characteristic of spherical particles. Furthermore, any manufacturing process for obtaining frozen particles with these desired characteristics should operate efficiently to offset the generally high cost of reagents and other raw materials.
Known techniques used in processing granular products include dry blending, direct compression, wet granulation, particle fabrication by coating product nuclei with discrete ingredients, and spray freezing of frozen particles.
Spray freezing methods generally produce highly uniform particles as a result of their characteristically rapid freezing processes. However, spray freezing is generally an expensive technique due to the high cost of refrigerants and the relatively large product losses which can occur.
Typical methods of spray freezing include striking or impinging a solution to be frozen into or against a liquid refrigerant stream(s) or spray(s), spraying a solution to be frozen onto the surface of a bath of liquid refrigerant, and spraying solution to be frozen through a freezing zone. Examples of refrigerants typically used to accomplish this freezing include liquid nitrogen, liquid carbon dioxide, and fluorocarbons.
German Patent No. 2,556,790 filed on Nov. 20, 1972 and published Jun. 6, 1974 discloses a process for deep freezing aqueous extracts with a freezing vessel having a conical lower section which provides for the impingement of a liquid product with a liquid refrigerant. Impingement occurs by one of three disclosed variations including downwardly spraying product and upwardly spraying refrigerants, upwardly spraying both product and liquid refrigerant, and both upwardly and downwardly spraying the product and upwardly spraying the liquid refrigerant. The disadvantage of this apparatus is the likelihood that frozen product will adhere to the liquid refrigerant nozzles and the funnel shaped bottom of the spray chamber, thus resulting in yield losses.
U.S. Pat. No. 4,952,224, issued Aug. 28, 1990, discloses an apparatus having a downwardly directed spray of atomized liquid fat and a radially inwardly directed plurality of individual spray jets of liquid nitrogen or carbon dioxide which surround and impinge against the downwardly directed spray of liquid fat droplets. The individual spray jets of this apparatus are likely to produce non-uniform agglomerations of the product due to the high velocity contact of the liquid refrigerant and the product. In addition, due to the limited time that the product is in contact with the liquid refrigerant, at least some product is unlikely to be frozen.
Italian Patent No. 2,659,546 issued Jul. 18, 1985, discloses an apparatus for freezing food products having an insulated freezing chamber with a conical lower section and a liquid refrigerant nozzle with a vertically downward directed spray located in the top center of the chamber. A plurality of product nozzles are distributed around and directed at the sides of the central refrigerant spray. Using this apparatus it is likely that unacceptably high particle size variations would occur during a continuous manufacturing process due to variations likely to occur in product supply and control systems, such as pressure changes in the product supply pump and pulsations within the nozzles.
U.S. Pat. No. 3,928,566 issued on Dec. 23, 1975 discloses an apparatus for freezing biological solutions in a moving stream of fluorocarbon refrigerant. The solutions are sprayed into this moving stream of fluorocarbon refrigerant from a plurality of small diameter syringe needles and the frozen particles are subsequently collected by skimming the surface of the bath with a collection device. This process has the disadvantage of forming particles of varying shape and uniformity. Further, the selection of the liquid refrigerant is critical to the use of the process because the density of it must be greater than the solution to be frozen to prevent the frozen particles from sinking below the surface of the liquid refrigerant bath. The use of fluorocarbon refrigerants, which provide for the buoyancy of the frozen particles, is nonetheless not desirable as a result of concerns relating to environmental emissions.
European Patent Application No. 0 478 118 published Apr. 1, 1992 discloses an apparatus that produces microfine particles for use in food processing, pharmaceuticals, and semiconductors having a freezing chamber with a conical lower section, a plurality of liquid refrigerant nozzles which direct the liquid refrigerant in a clockwise or counterclockwise direction within the vessel tangential to the circumference of the vessel, and a downwardly directed product nozzle. The disclosed apparatus has the disadvantage that at least some of the liquid refrigerant is likely to be in the form of relatively large droplets, and thus likely to be lost along the sides of the vessel.
There is needed an apparatus and process for producing uniformly, shaped, homogeneous frozen particles of a liquid while minimizing product yield losses.